Department of Endocrinology and Metabolism, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Internal Medicine, Copenhagen University Hospital Herlev Gentofte, Gentofte, Denmark.
Endocrine. 2021 Feb;71(2):467-475. doi: 10.1007/s12020-020-02507-x. Epub 2020 Oct 15.
Replicating the physiological cortisol secretion is key in the treatment of glucocorticoid insufficient individuals and optimization may enhance quality of life. The study investigates fatigue measured by ecological momentary assessments in patients treated with conventional hydrocortisone compared with once-daily dual-release hydrocortisone (Plenadren).
A 21-week open-label switch pilot trial included 30 patients with adrenal insufficiency due to hypopituitarism. Fatigue was assessed four times daily for 20 days using a momentary item version of the Multidimensional Fatigue Inventory on patients' usual hydrocortisone regimen. Participants switched treatment to an identical daily dose of Plenadren for 16 weeks where fatigue assessments were repeated. Change in fatigue and diurnal variation of fatigue was analyzed using mixed models for repeated measurements.
In four out of five fatigue subscales fatigue was significantly reduced 0.7-1.1 points (scales ranging from 4 to 20), when treated with Plenadren compared with conventional hydrocortisone, corresponding to small effect sizes below the scale-specific minimal important changes. However, 33% of the participants completing the study (9/27) experienced reductions in fatigue above the minimal important change. On Plenadren, we found larger between-person variances and smaller within-person variances. Finally, we identified diurnal fatigue curves for both treatments.
The Plenadren-related reduction in fatigue was significant but not necessarily of clinical importance when looking at a group level. However, there was a large interindividual variation in treatment effect, why patients with a large benefit in quality of life should be identified. Future RCTs should be powered to detect the effect magnitudes identified here.
复制生理皮质醇分泌是治疗糖皮质激素不足个体的关键，优化治疗可能会提高生活质量。本研究通过生态瞬时评估比较了传统氢化可的松与每日 1 次双释放氢化可的松（Plenadren）治疗的患者的疲劳情况。
这是一项为期 21 周的开放性标签转换先导试验，纳入了 30 名因垂体功能减退而导致肾上腺功能不全的患者。患者在接受常规氢化可的松治疗期间，使用多维疲劳量表的瞬时项目版，每天 4 次评估疲劳情况，共 20 天。参与者转换为每日相同剂量的 Plenadren 治疗 16 周，在此期间重复疲劳评估。使用重复测量混合模型分析疲劳变化和疲劳的日间变化。
在五个疲劳子量表中的四个中，与传统氢化可的松相比，Plenadren 治疗时疲劳显著降低了 0.7-1.1 分（量表范围为 4 到 20），对应于小于量表特定最小重要变化的小效应量。然而，完成研究的 27 名参与者中有 33%（9/27）经历了疲劳的降低超过了最小重要变化。在 Plenadren 治疗时，我们发现个体间差异较大，个体内差异较小。最后，我们确定了两种治疗方法的日间疲劳曲线。
Plenadren 相关的疲劳减轻具有统计学意义，但从群体水平来看，并不一定具有临床意义。然而，治疗效果存在很大的个体间差异，因此应该确定哪些患者的生活质量会有较大改善。未来的 RCT 应该有足够的效力来检测到这里确定的效应幅度。
